1. Field of Invention
This invention relates to pharmaceutical products containing a plurality of pharmaceutical dosage or diagnostic forms, and more particularly, to a product and method of making the product comprising a plurality of unit dosage or diagnostic forms with a controlled amount of at least one pharmaceutically or biologically active ingredient.
2. DESCRIPTION OF THE PRIOR ART
In the pharmaceutical industry, pharmaceutical products including diagnostic products comprise a container, e,g., a bottle, or a blister pack or other packages containing a plurality of unit dosage forms or diagnostic forms, each form containing a pharmaceutically or biologically active ingredient or ingredients and an inactive ingredient or ingredients. The pharmaceutically active ingredient typically forms a drug. The diagnostic form may comprise a reagent or the like for use in diagnostic tests. The diagnostic unit form may comprise an antibody, an antigen, or labeled forms thereof and so on. The diagnostic form may be part of a set which includes several different reagents or active ingredients.
The pharmaceutically or biologically active ingredient is combined with the inactive inert ingredient(s) to create the unit form, whether for pharmaceutical dosage or diagnostic purposes.
In solid pharmaceutical dosage forms, a pharmaceutically active ingredient may be supplied as a powder. In this format, each particle of the powder is formed of a given volume range of values to form a plurality of dry particles of a given pharmaceutically active ingredient amount.
The active ingredient particles are combined with inert or inactive ingredients to form major particles comprising combined inactive and pharmaceutically or biologically active ingredients. However, the amount of pharmaceutically or biologically active ingredient forming each major particle may vary significantly from particle to particle.
Typically, the major particles comprising both inactive and pharmaceutically and biologically active ingredients are then combined to create the final unit dosage or diagnostic form whether it be a tablet, caplet, test strip or capsule. Because the active and inactive particles and the major particles are in the order of micron volumes, a relatively large number of major particles of active and inactive ingredients are required to form the final unit pharmaceutical dosage or biological form.
Since the amount of active ingredient may vary significantly from major particle to major particle, a relatively large volume of such micron dimensioned major particles forming a unit form typically contains a wide range of active ingredients. Since such a wide range of ingredients would result in a final dosage or biological form that may be well above or below the desired dosage value of active ingredients, certain destructive analytical screening procedures are typically implemented by the prior art in an attempt to assess the variation of the amount of active ingredients in the final commercial unit dosage or biological forms.
The prior art employs destructive screening procedures which inspect the resulting unit dosage forms on a statistical basis. That is, the unit dosage forms are formed into batches or lot quantities. These batches or lot quantities of dosage forms are screened for the amount of active ingredient amounts on a sampling basis of the dosage forms. The screening used to measure the amount of dosage forms destroys the unit dosage forms and therefore must be limited to a sampling basis.
The sampling, being on a statistical basis, thus provides no assurance that all unit dosage forms in a given batch or lot are, in fact, within the desired content range of pharmaceutically or biologically active ingredients. There is always a percentage, based on statistics, of unit dosage or biological forms that exceed or fall short of the desired range of values of the unit dosage forms in each lot or batch. This lack of precise control of individual active ingredient content is recognized as undesirable.
In accordance with an aspect of the present invention, there is provided a product which comprises a package and a plurality of pharmaceutical or diagnostic unit dosage forms associated with the package, each unit dosage form including at least one active ingredient, the at least one active ingredient being present in each of the unit forms in an amount which does not vary from a predetermined amount by more than about 5%.
In one aspect, the unit forms are attached to laminated strips of substrate films.
In a further aspect, the package comprises a container and the dosage unit forms are solid and physically separate and independent from one another.
The dosage unit forms may be selected from the group consisting of any one of a tablet, caplet, a unit amount of active drug powder (for inhaler dosages and so on by way of example) and a capsule.
A method of forming a drug dosage or diagnostic product in a further aspect comprises forming a plurality of pharmaceutical or diagnostic unit dosage forms, each unit form including at least one active ingredient, the at least one active ingredient being present in each of the unit forms in an amount which does not vary from a predetermined amount by more than about 5%.
In a further aspect, the method includes laser scanning the unit forms in a raster scan to produce scan signals and calculating the amount of active ingredient in each unit form from the scan signals.
In a further aspect, the scanning may employ optical profilometry or diffuse reflection to produce the signals.
The method may include selectively discarding the unit form when the determined value of the deposited active ingredient exceeds or is less than a predetermined range of values.
The method may include non-destructively testing and may include calculating the amount of the at least one active ingredient in each unit form.
In a further aspect, the non-destructively testing includes measuring the thickness and area of the at least one active ingredient on a substrate corresponding to each unit form.
The non-destructively testing may include dividing the unit forms into a plurality of subgroups of unit forms and then discarding the unit forms of a selected subgroup a member of which is beyond the predetermined acceptable amount.
The predetermined acceptable amount preferably does not vary more than about 5% from a given value.
A diagnostic reagent kit according to a further aspect comprises a plurality of separate unit forms of a diagnostic reagent each unit form comprising a diagnostic reagent deposited on a substrate wherein the amount of diagnostic reagent in each unit form does not vary from a predetermined amount by more than 5%.
In a still further aspect, a method of making a pharmaceutical unit dosage or unit diagnostic form comprises depositing at least one pharmaceutically or diagnostic active ingredient on a substrate and then non-destructively determining the amount of deposited at least one active ingredient on the substrate.
The present invention is applicable to a package which includes separate units of diagnostic ingredients such as reagents for use in tests, antibodies, antigens and so on. The reagents may be part of a diagnostic unit which includes several different reagents.
With respect to a specific diagnostic reagent in a test, the test may include a plurality of separate units of the diagnostic reagent comprising the diagnostic reagent deposited on a substrate wherein the amount of diagnostic reagent in each unit does not vary from a predetermined amount by more than 5%. Each unit of the diagnostic reagent may be in a separate package or vial within a kit or may be separate independent units in a single package or vial in a kit.